Evidence map›Paper›PMID 21421874›Full record

ArticleInvestigative ophthalmology & visual science2011

Autophagy activation in the injured photoreceptor inhibits fas-mediated apoptosis.

Cagri G Besirli, Nicholas D Chinskey, Qiong-Duan Zheng, David N Zacks

Open access · bronzeAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Cagri G BesirliDepartment of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan 48105-0714, USA.
Nicholas D Chinskey
Qiong-Duan Zheng
David N Zacks

Funding

VIVARIUM MODULEP30EY007003 · NEI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI David Antonetti · 1987 to 2026
$17.6M
Molecular Regulation of Photoreceptor Cell DeathR01EY020823 · NEI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABCOUWER, STEVEN F, ZACKS, DAVID N · 2010 to 2023
$5.0M
E75 IN THE DEVELOPING DROSOPHILA EYEF31EY007003 · NEI · YALE UNIVERSITY · PI SHILTON, ALYCIA N · 1999 to 2001
$14k
NEI NIH HHS F31 EY007003NEI NIH HHS NEI-EY-07003NEI NIH HHS P30 EY007003NEI NIH HHS R01 EY020823PHS HHS R01-020823
6 · The paper itself

Abstract

purposeTo examine the activation of autophagy and its relationship to Fas-mediated photoreceptor apoptosis during experimental retinal detachment.

methodsRetina-retinal pigment epithelium (RPE) separation was created in Brown-Norway rats by subretinal injection of 1% hyaluronic acid and the intraretinal levels of the autophagy proteins LC3 and Atg5, the time course of LC3-I to LC3-II conversion, and the activation of cathepsins B and D were assayed with Western blot analysis and immunohistochemistry. We measured the ability of a Fas-activating antibody to induce LC3-I to LC3-II conversion in 661W cells, and the in vivo effect of Met12, a small molecule inhibitor of the Fas receptor, on LC3-I to LC3-II conversion and Atg5 expression. Autophagy activation was inhibited using 3-methyladenine (3-MA) or siRNA knockdown of Atg5 and the effect on apoptosis was measured using a caspase 8 activity assay, caspase 8 immunoblots, and photoreceptor TUNEL staining.

resultsRetina-RPE separation resulted in a Fas-dependent activation of autophagy, with increased Atg5 levels and intraphotoreceptor conversion of LC3-I to LC3-II. Detached retinas had increased levels of autophagosome-associated lysosomal proteases, cathepsins B and D. Inhibition of autophagy by 3-MA or siAtg5 accelerated the time course of caspase 8 activation and photoreceptor TUNEL staining.

conclusionsAutophagy activation occurs in the photoreceptors after retina-RPE separation. This appears to be, at least in part, dependent on Fas receptor activation, and plays a role in regulating the level of photoreceptor apoptosis.

Indexed as

ApoptosisAutophagyPhotoreceptor Cells, VertebrateAdenineAnimalsAutophagy-Related Protein 5Blotting, WesternCaspase 8Cathepsin BCathepsin DCell LineEnzyme Activationfas ReceptorImmunohistochemistryMaleMicrotubule-Associated Proteins3-methyladenineAdenineAnxa3 protein, ratAtg5 protein, ratAutophagy-Related Protein 5Casp8 protein, ratCaspase 8Cathepsin BCathepsin DCtsb protein, ratCtsd protein, ratfas ReceptorMicrotubule-Associated ProteinsProtein IsoformsProteinsRNA, Small Interfering

Identifiers

PMID21421874
PMCPMC3175961
OpenAlexW2077474963

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.